Kinase Isoenzyme MB Research Articles

A-015 Changes of sST2 and NT-proBNP levels predict early cardiovascular toxicity in breast cancer patients treated with anthracycline-containing chemotherapy

Abstract Background Cardiovascular biomarkers play a crucial role in monitoring the risk for cancer therapy-related cardiovascular toxicity, but their changes and values at the early stage of chemotherapy are still inadequate, especially for some new biomarkers.The purpose of this study was to examine changes in cardiovascular biomarkers and evaluate the prognostic values for cardiovascular toxicity in patients with breast cancer treated with anthracycline-containing chemotherapy. Methods In a prospective cohort of 73 patients treated with anthracycline-containing chemotherapy, soluble ST2 (sST2), high-sensitivity cardiac troponin T (hs-cTnT), N-terminal pro-B-type natriuretic peptide (NT-proBNP), Myoglobin (Myo), Creatine kinase isoenzyme MB (CK-MB) and heart-fatty acid binding protein (H-FABP) were measured at baseline, during every chemotherapy cycle (C1-C6, about every month).Cardiovascular toxicity was defined as cancer therapy-related arrhythmias, which was differentiated into bradycardia,tachycardia or atrial fibrillation. According to whether arrhythmia occurred, patients were divided into two groups (healthy group and arrhythmias group), and the basic clinical characteristics were collected and compared among the two groups. Logistic regression analyses and receiver operating characteristic (ROC) curves were conducted to investigate the relationship between the changes in biomarkers and anthracycline-induced cardiotoxicity. Results sST2 levels increased significantly from baseline to C1 (P<0.01). NT-proBNP decreased from baseline to C1, C5 (P< 0.01). Logistic regression analysis showed a greater risk of cardiovascular toxicity was associated with greater interval increase in sST2 from baseline to C1(ΔsST2) (OR:1.27; 95% CI:1.03 to1.56; P= 0.024) and interval decline in NT-proBNP from baseline to C1(ΔNT-proBNP) was associated with cardiovascular toxicity (OR: 0.83; 95% CI: 0.70 to 0.98; P= 0.029). ROC curves showed that ΔsST2, ΔNT-proBNP and ΔsST2+ΔNT-proBNP had good predictive value for cardiovascular toxicity (areas under the curves were 0.631, 0.633, and 0.735, respectively, P<0.05). Conclusions Early changes in sST2 and NT-proBNP levels offer additive information in early cardiovascular toxicity risk prediction in patients with breast cancer who receive anthracycline-containing chemotherapy.

Protective effects of silymarin against paclitaxel-induced cardiac toxicity

In this study, the protectivity of silymarin (SY) against the harmful effects of paclitaxel (PX) on the heart was investigated. PX was administered 2 mg/kg intraperitoneally to the PX group, 100 mg/kg SY wasadministered by gavage to the SY group, and both drugs were administered to the PX + SY group as other groups. Treatment with SY significantly decreased cardiac troponin I (cTn-I), brain natriuretic peptide (BNP), creatine kinase isoenzyme MB (CK-MB) and lactate dehydrogenase (LDH) levels. In the PX group; the decrease in glutathione (GSH), catalase (CAT) and superoxide dismutase (SOD) levels and the increase in malondialdehyde (MDA) levels were significantly normalized with SY administration. Histologically; heart injury was significantly reduced in the PX + SY group compared to the PX group. As a result, it was determined that SY, which has antioxidant, anti-apoptotic and anti-inflammatory effects, could protect the heart tissue from the toxic effects of PX.

The Value of Biomarkers in Major Cardiovascular Surgery Necessitating Cardiopulmonary Bypass.

The use of biomarkers in cardiovascular surgery is an evolving field with promising potential; however, current research remains largely limited, requiring further validation for routine clinical application. This review explores the application of biomarkers in cardiovascular surgery, focusing on heart failure, cardiac ischemia, and organ dysfunction, including renal, cerebral, pulmonary, and splanchnic impairments. Additionally, it examines the significance of biomarkers in assessing the inflammatory state and oxidative stress during the perioperative period, particularly in the context of major surgical trauma and cardiopulmonary bypass (CPB). From January 2018 to June 2024, we reviewed 133 studies and four systematic reviews and meta-analyses using the Medline, Embase, and Central databases, screening for pre- or postoperative biomarker levels in patients undergoing cardiac surgery. Outcomes of interest were postoperative mortality, nonfatal myocardial infarction, stroke, congestive heart failure, and major adverse cardiovascular events (MACEs). Studies reporting multivariable-adjusted risk estimates were included. The findings revealed that cardiac troponins (cTns) and creatine kinase isoenzyme MB (CK-MB) remain the most widely utilized biomarkers for assessing myocardial injury post-surgery. These elevated biomarker levels were consistently associated with an increased risk of postoperative complications, including low cardiac output syndrome, prolonged ventilation, and mortality. Emerging biomarkers, such as heart-type fatty acid-binding protein (h-FABP) and high-sensitivity C-reactive protein (hs-CRP), demonstrated promising early detection and risk stratification results. In particular, h-FABP increased rapidly within one hour of myocardial injury, peaking at 4-6 hours and returning to baseline within 24 hours. This rapid clearance makes h-FABP a valuable tool for early myocardial injury detection, potentially allowing for timely interventions. Inflammatory biomarkers, including hs-CRP and pentraxin 3 (PTX3), were found to be associated with poor outcomes, such as increased morbidity and mortality. Elevated preoperative levels of these markers were indicative of a heightened inflammatory response, correlating with worse postoperative recovery and higher rates of complications. Furthermore, the neutrophil-to-lymphocyte ratio (NLR) emerged as a cost-effective and easily accessible predictor of postoperative outcomes. Elevated NLR values were linked to an increased risk of adverse events, including prolonged ventilation, low cardiac output syndrome, and overall mortality. Further, the practicality of measuring NLR through routine blood tests makes it viable for widespread clinical use. In conclusion, integrating biomarkers in cardiovascular surgery significantly advances predicting postoperative outcomes for cardiac surgery patients. Therefore, it is essential to categorize these biomarkers into two distinct groups in the future, inflammatory and non-inflammatory (related to organ damage), to improve understanding and enhance their clinical applicability. Future research should focus on standardizing the use of these biomarkers and exploring their combined predictive power to enhance risk stratification and improve patient prognosis.

Effectiveness of different tirofiban administration times in patients with no-reflow myocardial infarction during percutaneous coronary intervention.

To compare the effectiveness of different tirofiban administration time windows in patients with no-reflow myocardial infarction (MI) during percutaneous coronary intervention (PCI). This single centre retrospective observational study included patients with no-reflow MI, undergoing PCI at the Hanyang Hospital affiliated to Wuhan University of Science and Technology from March 2020 to May 2023. All patients were administered tirofiban. Patients who received tirofiban with postinterventional thrombolysis in myocardial infarction (TIMI) flow ≥ 1 were grouped as Group-I, and patients who were directly given tirofiban through the guiding catheter without forward blood flow were grouped as Group-II. TIMI blood flow classification, levels of cardiac troponin T (cTnT) and creatine kinase isoenzyme MB (CK-MB), incidence of complications and major adverse cardiovascular events (MACE) in the two groups before and after the treatment were statistically analyzed. A total of 156 patients were included in this study, including 79 patients in Group-I and 77 patients in Group-II. There was no significant difference in the baseline data between the two groups (P>0.05). After treatment, TIMI blood flow classification of the two groups improved and was significantly better in Group-I compared to Group-II (P<0.05). After treatment, levels of Serum cTnT and CK-MB in the two groups decreased, and were significantly lower in Group-I than in Group-II (P<0.05). There was no significant difference in the incidence of complications between Group-I (3.80%) and Group-II (6.49%) (P>0.05). The incidence of MACE in Group-I (3.80%) was lower than that in Group-II (12.99%) (P<0.05). Compared with the direct application of tirofiban, tirofiban given when TIMI Grade≥ 1 for patients with no-reflow MI during PCI can more effectively regulate the blood flow status of target vessels, reduce myocardial injury, and reduce the risk of MACE.

Effect of Linggui Zhugan Decoction on myocardial fibrosis and Lats1/Yap signaling pathway in mice after myocardial infraction

This study aims to investigate the effects of Linggui Zhugan Decoction(LGZGD) on myocardial fibrosis(MF) and the Lats1/Yap signaling pathway in mice after myocardial infarction(MI), exploring its role and mechanism in inhibiting MF. The MI-induced ischemic mouse model was established by left anterior descending coronary artery ligation, followed by continuous intervention for six weeks. Doppler ultrasound imaging-system of small animals was used to detect left ventricular ejection fraction(LVEF), left ventricular fractional shortening(LVFS), left ventricular internal diameter at end-systole(LVIDs), and left ventricular internal diameter at end-diastole(LVIDd). Pathological changes in myocardial tissue were observed by HE and Masson staining. Serum levels of creatine kinase isoenzyme MB(CK-MB) and lactate dehydrogenase(LDH) were detected by using ELISA. Myocardial tissue mRNA levels of Lats1, Yap, and connective tissue growth factor(CTGF) were determined by RT-qPCR. Protein expression of alpha-smooth muscle actin(α-SMA), collagen Ⅰ(Col Ⅰ), collagen Ⅲ(Col Ⅲ), tissue inhibitor of metal protease 1(TIMP1), matrix metallopeptidase 2(MMP2), Yap, p-Yap, and n-Yap was determined by Western blot. Compared with the sham group, the model group showed significantly decreased LVEF and LVFS levels, increased LVIDd and LVIDs levels(P&lt;0.01), disordered arrangement of myocardial cells, partial fracture of myocardial fibers, and massive deposition of collagen fibers. Moreover, serum levels of CK-MB and LDH were significantly increased(P&lt;0.01), while myocardial tissue mRNA levels of Lats1 were significantly decreased(P&lt;0.01), and mRNA levels of Yap and CTGF were significantly increased(P&lt;0.01). Protein expression of α-SMA, Col Ⅰ, Col Ⅲ, MMP2, Yap, and n-Yap was significantly increased(P&lt;0.01), while protein expression of Lats1, TIMP1, p-Yap, and the ratio of p-Yap/Yap were significantly decreased(P&lt;0.01). Compared with the model group, after intervention with LGZGD(9.36 g·kg~(-1)), mice showed significantly increased LVEF and LVFS levels, decreased LVIDd and LVIDs levels(P&lt;0.01), more orderly arrangement of myocardial cells, significantly reduced myocardial fiber fracture and collagen fiber deposition. Serum levels of CK-MB and LDH were significantly decreased(P&lt;0.01), while myocardial tissue mRNA levels of Lats1 were significantly increased(P&lt;0.01), and mRNA levels of Yap and CTGF were significantly decreased(P&lt;0.01). Protein expression of α-SMA, Col Ⅰ, Col Ⅲ, MMP2, Yap, and n-Yap was significantly decreased(P&lt;0.01), while protein expression of Lats1, TIMP1, p-Yap, and the ratio of p-Yap/Yap were significantly increased(P&lt;0.01). LGZGD can inhibit MF in mice after MI and improve mouse cardiac function, which is closely related to the activation of the Lats1/Yap signaling pathway.

Effect and mechanism of T lymphocytes on human induced pluripotent stem cell-derived cardiomyocytes via Proteomics

BackgroundAbnormalities in T cell activation play an important role in the pathogenesis of myocarditis, and persistent T cell responses can lead to autoimmunity and chronic cardiac inflammation, as well as even dilated cardiomyopathy. Although previous work has examined the role of T cells in myocarditis in animal models, the specific mechanism for human cardiomyocytes has not been investigated.MethodsIn this study, we constructed the human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and established the T cell-mediated cardiac injury model by co-culturing with activated CD4 + T or CD8 + T cells that were isolated from peripheral mononuclear blood to elucidate the pathogenesis of myocardial cell injury caused by inflammation.ResultsBy combination of quantitative proteomics with tissue and cell immunofluorescence examination, we established a proteome profile of inflammatory myocardia from hiPSC-CMs with obvious cardiomyocyte injury and increased levels of lactate dehydrogenase content, creatine kinase isoenzyme MB and cardiac troponin. A series of molecular dysfunctions of hiPSC-CMs was observed and indicated that CD4 + cells could produce direct cardiomyocyte injury by activating the NOD-like receptor signals pathway.ConclusionsThe data presented in our study established a proteome map of inflammatory myocardial based on hiPSC-CMs injury model. These results can provide guidance in the discovery of improved clinical treatments for myocarditis.

Oxycodone attenuates lipopolysaccharide-induced myocardial injury by inhibiting inflammation, oxidation and pyroptosis via Nrf2/HO-1 signalling pathway.

Myocardial injury and cardiovascular dysfunction are the most common complications of sepsis, and effective therapeutic candidate is still lacking. This study aims to investigate the protective effect of oxycodone in myocardial injury of lipopolysaccharide-induced sepsis and its related signalling pathways. Wild-type and nuclear factor erythroid 2-related factor 2 (Nrf2)-knockout mice, as well as H9c2 cardiomyocytes cultures treated with lipopolysaccharide (LPS) were used as models of septic myocardial injury. H9c2 cardiomyocytes culture showed that oxycodone protected cells from pyroptosis induced by LPS. Mice model confirmed that oxycodone pretreatment significantly attenuated myocardial pathological damage and improved cardiac function demonstrated by increased ejection fraction (EF) and fractional shortening (FS), as well as decreased cardiac troponin I (cTnI) and creatine kinase isoenzymes MB (CK-MB). Oxycodone also reduced the levels of inflammatory factors and oxidative stress damage induced by LPS, which involves pyroptosis-related proteins including: Nod-like receptor protein 3 (NLRP3), Caspase 1, Apoptosis-associated speck-like protein contain a CARD (ASC), and Gasdermin D (GSDMD). These changes were mediated by Nrf2 and heme oxygenase-1 (HO-1) because Nrf2-knockout mice or Nrf2 knockdown in H9c2 cells significantly reversed the beneficial effect of oxycodone on oxidative stress, inflammatory responses and NLRP3-mediated pyroptosis. Our findings yielded that oxycodone therapy reduces LPS-induced myocardial injury by suppressing NLRP3-mediated pyroptosis via the Nrf2/HO-1 signalling pathway in vivo and in vitro.

Feasibility of aligning creatine kinase MB activity and mass data in multicentre trials using generalized additive modelling.

Elevated serum creatine kinase isoenzyme MB (CK-MB) levels indicate myocardial ischaemia and periprocedural myocardial injury during treatment of heart diseases. We established a method to predict CK-MB mass from activity data based on a prospective pilot study in order to simplify multicentre trials. 38 elective cardiac surgery patients without acute myocardial ischaemia and terminal renal failure were recruited. CK-MB mass and activity were determined in venous blood samples drawn preoperatively, postoperatively, 6 h post-op, and 12 h post-op. Linear regression and generalized additive models (GAMs) were applied to describe the relationship of mass and activity. Influences of demographic and perioperative factors on the fit of GAMs was evaluated. The agreement of predicted and measured CK-MB masses was assessed by Bland-Altman analyses. Linear regression provided an acceptable overall fit (r2 = 0.834) but showed deviances at low CK-MB levels. GAMs did not benefit from the inclusion of age, body mass index and surgical times. The minimal adequate model predicted CK-MB masses from activities, sex and sampling time with an r2 of 0.981. Bland-Altman analyses confirmed narrow limits of agreement (spread: 8.87 µg/l) and the absence of fixed (P = 0.41) and proportional (P = 0.21) biases. GAM-based modelling of CK-MB data in a representative patient cohort allowed to predict CK-MB masses from activities, sex and sampling time. This approach simplifies the integration of study centres with incompatible CK-MB data into multicentre trials in order to facilitate inclusion of CK-MB levels in statistical models.

Combined Intracoronary Prourokinase Thrombolysis on Myocardial Perfusion and Vascular Endothelial Function in STEMI.

This study aimed to investigate the effects of intracoronary prourokinase thrombolysis combined with emergency percutaneous coronary intervention (PCI) on myocardial perfusion and vascular endothelial function in patients with acute ST-segment elevation myocardial infarction (STEMI). A total of 104 patients with STEMI were collected from August 2020 to August 2022, and were divided into control group and observation group in a random manner. The control group received PCI directly, and the observation group received intracoronary prourokinase thrombolytic therapy before PCI. The treatment effects were evaluated by measuring the cardiac function indexes, including left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), and left ventricular ejection fraction (LVEF), the TIMI myocardial perfusion grade, the vascular endothelial indexes, including soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1), the von Willebrand factor (vWF), the myocardial injury indexes, including cardiac troponin I (cTnI), creatine kinase isoenzyme MB (CK-MB), and lactate dehydrogenase (LDH), and the inflammatory factors, including myeloperoxidase (MPO), C-reactive protein (CRP), and interleukin-6 (IL-6). Furthermore, the treatment safety was assessed by recording the incidence of major MACE events, 6 months after the operation. After treatment, LVEDD and LVESD were lower in the observation group than in the control group, and LVEF was higher (p < 0.05). The TIMI myocardial perfusion grade in the observation group was higher than in the control group, after treatment (p < 0.05). The levels of sICAM-1, sVCAM-1, and vWF were higher in the observation group than in the control group (p < 0.05). The levels of cTnI, CK-MB, and LDH in the observation group were lower than those in the control group, 24 hours after surgery. At 3 days after surgery, MPO was lower in the observation group than in the control group, and CRP and IL-6 were higher (p < 0.05). The incidence of major MACE events in the observation group was lower than that in the control group, 6 months after surgery (p < 0.05). There was 1 case of puncture site bleeding in the observation group, 1 case of puncture site bleeding and 1 case of subcutaneous ecchymosis in the control group, but no serious bleeding events, such as internal bleeding or cerebral hemorrhage, in the two groups. Intracoronary prourokinase thrombolytic therapy combined with emergency PCI can promote the recovery of cardiac function, improve myocardial perfusion and vascular endothelial function, and reduce inflammation and the incidence of major postoperative MACE events in acute STEMI patients.

Simultaneous ST-elevation in lead augmented vector right (aVR) and III in non-ST-elevation acute coronary syndromes.

The value of ST-elevation in lead augmented vector right (aVR) remains controversial in clinical practice. This study aimed to investigate the association of simultaneous ST-elevation in lead aVR and III with angiographic findings and clinical outcomes in patients with non-ST-elevation acute coronary syndromes (NSTEACS). In this observational study, patients who had been diagnosed with NSTEACS and presented with ST-elevation in lead aVR and without ST-elevation in any other two contiguous leads were enrolled from January 2018 to June 2019. Demographic, baseline clinical, angiographic and interventional characteristics as well as clinical outcomes were collected and recorded on standardized case report forms. A total of 157 patients meeting the criteria were finally enrolled in this study and classified into two groups according to the presence of ST-elevation in lead III. Patients in the two groups were similar in average age and previous history of hypertension, diabetes mellitus, hyperlipidemia, chronic kidney disease, stroke, and peripheral vascular diseases (all P>0.05). Patients with ST-elevation in lead III tended to present with myocardial hypertrophy in the echocardiography (P=0.02). The cases with ST-elevation in lead III showed higher high sensitivity troponin T (hs-TnT; P=0.08) and creatinine kinase MB isoenzyme (CK-MB; P<0.01) whereas those without ST-elevation in lead III showed higher N-terminal pro brain natriuretic peptide (NT-proBNP; P=0.02). Of note, patients with ST-elevation in lead III presented with more ST-depression in multiple leads [especially in lead I, augmented vector left (aVL), V3-V6] as well as higher degree of ST-depression (all P<0.05) and were more likely to develop multi-vessel and left main trunk (LM) lesions (P=0.04), with 20% of the cases having a LM lesion and 60% having triple vessel lesions. Patients with ST-elevation in lead III were at increased risk of 3-year major adverse cardiovascular events (MACEs), despite no significant statistical difference between the two groups (hazard ratio =1.29; P=0.26). The NSTEACS cases with simultaneous ST-elevation in lead III and aVR tended to present with more multiple leads with ST-depression, higher degree of ST-depression, and more LM or multi-vessel lesions, suggesting a broader range of severe myocardial ischemia. The concurrent presentation of ST-elevation in lead III and aVR may play a vital role in the diagnosis, risk-stratification, and prediction of poor prognosis during the management of NSTEACS patients.

A Retrospective Study of Whether Sacubitril–Valsartan Improves Cardiac Function in Patients with Acute Coronary Syndrome and Hypertension after Percutaneous Coronary Intervention

Objectives: This study aimed to explore the effect of sacubitril–valsartan on cardiac function in patients with acute coronary syndrome (ACS) and hypertension after percutaneous coronary intervention (PCI). Methods: The study was conducted on 166 patients with ACS and hypertension who underwent PCI at our hospital from July 2022 to June 2023. The patients were divided into two groups: an observation group and a control group, with 83 cases in each group. The observation group was given sacubitril–valsartan, and the control group was given enalapril. The treatment period was 3 months. The cardiac function indexes, biochemical indexes, adverse reactions, and the occurrence of new cardiovascular and cerebrovascular events were compared between the two groups before and after medication. Results: We found no statistically dramatic differences between the two groups in gender, age, body mass index, diabetes, hyperlipidemia, family history of ACS, family history of hypertension, smoking history, drinking history, regular exercise history, low-salt and low-fat diet, New York Heart Association cardiac function classification, number of vessels involved in coronary artery disease, stent length, stent inner diameter, number of stent implants, duration of hypertension, medication time, use of antihypertensive drugs, systolic blood pressure (SBP), and diastolic blood pressure (DBP). The observation group had lower left ventricular end-diastolic internal diameter (LVEDD) levels, higher left ventricular ejection fraction (LVEF) levels, and lower left ventricular end-systolic internal diameter (LVESD) levels compared with the control group. The levels of N-terminal pro-brain B-type natriuretic peptide (NT-proBNP), cardiac troponin I (cTnI), and creatine kinase isoenzyme MB (CK-MB) in the observation group decreased compared with those in the control group. Compared with the pre-medication period, LVEDD levels decreased, LVEF levels increased, and LVESD levels decreased in the observation and control groups, whereas NT-proBNP, cTnI, and CK-MB levels decreased in the observation and control groups. The total incidence rates of adverse reactions and new cardiovascular and cerebrovascular events in the observation group were found to be lower than those in the control group. Conclusion: The application of sacubitril–valsartan in patients with ACS complicated with hypertension after PCI can effectively improve patients' cardiac function, reduce biochemical indexes related to myocardial injury, and lower the incidence of adverse cardiovascular events. It features good safety, providing a new treatment strategy and method for patients with ACS complicated with hypertension.

The possible association of mitochondrial fusion and fission in copper deficiency-induced oxidative damage and mitochondrial dysfunction of the heart

IntroductionAs an essential trace element, Copper (Cu) participates in numerous physiological and biological reactions in the body. Cu is closely related to heart health, and an imbalance of Cu will cause cardiac dysfunction. The research aims to examine how Cu deficiency affects the heart, assess mitochondrial function in the hearts, and disclose possible mechanisms of its influence. MethodsWeaned mice were fed Cu-deficient diets and intraperitoneally given copper sulfate (CuSO4) to correct the Cu deficiency. The pathological change of the heart was assessed using histological inspection. Cardiac function and oxidative stress levels were evaluated by biochemical assay kits. ELISA and ATP detection kits were used to detect the levels of complexes I-IV in the mitochondrial respiratory chain (MRC) and ATP, respectively. Real time PCR was utilized to determine mRNA expressions, and Western blotting was adopted to determine protein expressions, of molecules related to mitochondrial fission and fusion. ResultsCu deficiency gave rise to elevated heart index, cardiac histological alterations and oxidation injury, increased serum levels of creatine kinase (CK), lactic dehydrogenase (LDH), and creatine kinase isoenzyme MB (CK-MB) together with increased malondialdehyde (MDA) production, decreased the glutathione (GSH), Superoxide Dismutase (SOD), and Catalase (CAT) activities or contents. Besides, Cu deficiency caused mitochondrial damage characterized by decreased contents of complexes I-IV in the MRC and ATP in the heart. In the meantime, Cu deficiency also reduced protein and mRNA expressions of factors associated with mitochondrial fusion, including Mfn1 and Mfn2, while significantly increased factors Drip1 and Fis1 related to mitochondrial fission. However, adding CuSO4 improved the above changes significantly. ConclusionAccording to research results, Cu deficiency can cause heart damage in mice, along with oxidative damage and mitochondrial dysfunction, which are closely related to mitochondrial fusion and fission disorders.

The Relationship Between Changes of Left Heart Structure and Function and the Risk of Future Renal Damage in Patients with Essential Hypertension.

In essential hypertensive patients, cardiac remodeling may be associated with the risk of renal damage in the future which can be reflected by the estimated glomerular filtration rate (eGFR). Through retrospective analysis, we evaluated the potential of cardiac remodeling based on echocardiographic measurements to predict the risk of renal damage in the future with hypertensive patients. We retrospectively analyzed the relationship between the changes of left heart structure and function and renal damage for 510 patients with hypertension, who were diagnosed between 2016 to 2022. Demography data, clinical data, blood samples and echocardiographic variables were used for survival analysis, and the Cox proportional hazards regression model was used. In our study, we found that age, serum creatinine (SCR), creatine kinase isoenzyme MB (CK MB), abnormal high-sensitivity troponin I (TNI), interventricular septum thickness (IVST) and left ventricular ejection fraction (LVEF) could be used as independent predictors in risk of renal impairment in hypertensive patients (p<0.05). Combined in a score where one point was given for the presence of each of the parameters above, this score could strongly predict renal function damage in the future (p<0.05). In receiver operating characteristics (ROC) curve analyses, the area under the curve of the risk factor score was 0.849 (P<0.001). In essential hypertensive patients, LVEF and IVST can predict the risk of future adverse renal outcomes. Moreover, combining risk variables into a simplified score may enable to assess the risk of renal impairment in hypertensive patients at an early stage.

Platycodin D Ameliorates Type 2 Diabetes-Induced Myocardial Injury by Activating the AMPK Signaling Pathway.

The current study aimed to assess the effectiveness of pharmacological intervention with Platycodin D (PD), a critically active compound isolated from the roots of Platycodon grandiflorum, in mitigating cardiotoxicity in a murine model of type 2 diabetes-induced cardiac injury and in H9c2 cells in vitro. Following oral administration for 4 weeks, PD (2.5 mg/kg) significantly suppressed the elevation of fasting blood glucose (FBG) levels, improved dyslipidemia, and effectively inhibited the rise of the cardiac injury markers creatine kinase isoenzyme MB (CK-MB) and cardiac troponin T (cTnT). PD treatment could ameliorate energy metabolism disorders induced by impaired glucose uptake by activating AMPK protein expression in the DCM mouse model, thereby promoting the GLUT4 transporter and further activating autophagy-related proteins. Furthermore, in vitro experiments demonstrated that PD exerted a concentration-dependent increase in cell viability while also inhibiting palmitic acid and glucose (HG-PA)-stimulated H9c2 cytotoxicity and activating AMPK protein expression. Notably, the AMPK activator AICAR (1 mM) was observed to upregulate the expression of AMPK in H9c2 cells after high-glucose and -fat exposure. Meanwhile, we used AMPK inhibitor Compound C (20 μM) to investigate the effect of PD activation of AMPK on cells. In addition, the molecular docking approach was employed to dock PD with AMPK, revealing a binding energy of -8.2 kcal/mol and indicating a tight interaction between the components and the target. PD could reduce the expression of autophagy-related protein p62, reduce the accumulation of autophagy products, promote the flow of autophagy, and improve myocardial cell injury. In conclusion, it has been demonstrated that PD effectively inhibits cardiac injury-induced type 2 diabetes in mice and enhances energy metabolism in HG-PA-stimulated H9c2 cells by activating the AMPK signaling pathway. These findings collectively unveil the potential cardioprotective effects of PD via modulation of the AMPK signaling pathway.

Prediction model for developing neuropsychiatric systemic lupus erythematosus in lupus patients.

This study aimed to construct a predictive model for assessing the risk of development of neuropsychiatric systemic lupus erythematosus (NPSLE) among patients with SLE based on clinical, laboratory, and meteorological data. A total of 2232 SLE patients were included and were randomly assigned into training and validation sets. Variables such as clinical and laboratory data and local meteorological data were screened by univariate and least absolute shrinkage and selection operator (LASSO) logistic regression modelling. After 10-fold cross-validation, the predictive model was built by multivariate logistic regression, and a nomogram was constructed to visualize the risk of NPSLE. The efficacy and accuracy of the model were assessed by receiver operating characteristic (ROC) curve and calibration curve analysis. Net clinical benefit was assessed by decision curve analysis. Variables that were included in the predictive model were anti-dsDNA, anti-SSA, lymphocyte count, hematocrit, erythrocyte sedimentation rate, pre-albumin, retinol binding protein, creatine kinase isoenzyme MB, Nterminal brain natriuretic peptide precursor, creatinine, indirect bilirubin, fibrinogen, hypersensitive C-reactive protein, CO, and mild contamination. The nomogram showed a broad prediction spectrum; the area under the curve (AUC) was 0.895 (0.858-0.931) for the training set and 0.849 (0.783-0.916) for the validation set. The model exhibits good predictive performance and will confer clinical benefit in NPSLE risk calculation. Key Points • Clinical, laboratory, and meteorological data were incorporated into a predictive model for neuropsychiatric systemic lupus erythematosus (NPSLE) in SLE patients. • Anti-dsDNA, anti-SSA, LYM, HCT, ESR, hsCRP, IBIL, PA, RBP, CO, Fib, NT-proBNP, Crea, CO, and mild contamination are predictors of the development of NPSLE and may have potential for research. • The nomogram has good predictive performance and clinical value and can be used to guide clinical diagnosis and treatment.

Comparison of modified Del Nido and Custodiol® cardioplegia in minimally invasive mitral valve surgery.

In this study, we evaluated if modified Del Nido cardioplegia delivers comparable cardiac protection in comparison to Custodiol® in patients undergoing isolated minimally invasive mitral valve repair. From January 2018 to October 2021, all patients undergoing non-emergent isolated minimally invasive mitral valve repair were included in this study. The cardioplegia was chosen at the surgeons' discretion. The primary end points of this study were peak postoperative cardiac enzyme levels. Secondary end points were in-hospital mortality, hospital stay, occurrence of cardiac arrhythmias, pacemaker implantations, postoperative lactate and sodium levels and postoperative incidence of renal failure requiring dialysis. A total of 355 patients were included in this study. The mean age of patients was 57. After propensity score matching, a total of 156 pairs were identified. There was no difference in cross-clamp time between both groups. Postoperative creatine kinase levels were higher in patients receiving Custodiol on the 1st and 2nd postoperative days. Creatine kinase isoenzyme MB levels were higher in patients receiving Custodiol on the 2nd postoperative day (0.5 ± 0.2 vs 0.4 ± 0.1 µmol/l s; P < 0.001). Postoperative Troponin T concentrations were similar between both groups. Maximum lactate concentrations were higher in patients receiving Custodiol on the day of surgery (2.4 ± 1.9 vs 2.0 ± 1.1 mmol/l; P = 0.04). The overall hospital stay was longer in patients receiving Del Nido cardioplegia (10.6 ± 3.2 vs 8 ± 4.1 days; P < 0.01). Modified Del Nido cardioplegia based on Ionosteril® solution offers equivalent protection compared to Custodiol for isolated minimally invasive mitral valve repair.

Analysis of risk factors and changes in myocardial biomarker levels in 122 cases of early neonatal anemia.

Anemia in the first week after birth, which could affect growth, development, and organ function, should be an important warning sign to clinicians. The aim of this study was to assess the related risk factors of early neonatal anemia and to analyze the effect of anemia on the expression levels of myocardial markers in newborns. Clinical data from 122 confirmed cases of anemic newborns and 108 nonanemic newborns were collected to analyze the independent risk factors for early anemia using logistic regression analyses. Blood samples were collected from both groups for the detection of myocardial markers, including the protein marker cardiac troponin T (cTnT), as well as enzyme markers creatine kinase isoenzyme MB (CK-MB) and lactate dehydrogenase (LDH). Multivariate logistic regression analysis revealed that preterm birth (OR: 3.589 [1.119-11.506], p < 0.05), multiple pregnancy (OR: 4.117 [1.021-16.611], p < 0.05), and abnormal placenta (OR: 4.712 [1.077-20.625], p < 0.05) were independent risk factors for early neonatal anemia. The levels of myocardial markers, including cTnT (303.1 ± 244.7 vs. 44.2 ± 55.41 ng/L), CK-MB (6.803 ± 8.971 vs. 2.5326 ± 2.927 μkat/L), and LDH (32.42 ± 35.26 vs. 19.73 ± 17.13 μkat/L), were significantly higher in the anemic group than in the nonanemic group. Multiple pregnancy, preterm birth, and abnormal placenta were identified as risk factors for early neonatal anemia. The occurrence of early neonatal anemia was associated with increased levels of myocardial markers.

Dexmedetomidine Pretreatment Confers Myocardial Protection and Reduces Mechanical Ventilation Duration for Patients Undergoing Cardiac Valve Replacement under Cardiopulmonary Bypass.

The study aims to assess the effects of dexmedetomidine (Dex) pretreatment on patients during cardiac valve replacement under cardiopulmonary bypass. For patients in the Dex group (n = 52), 0.5 μg/kg Dex was given before anesthesia induction, followed by 0.5 μg/kg/h pumping injection before aortic occlusion. For patients in the control group (n = 52), 0.125 ml/kg normal saline was given instead of Dex. The patients in the Dex group had longer time to first dose of rescue propofol than the control group (P = 0.003). The Dex group required less total dosage of propofol than the control group (P = 0.0001). The levels of cardiac troponin I (cTnI), creatine kinase isoenzyme MB (CK-MB), malondialdehyde (MDA), and tumor necrosis factor-α (TNF-α) were lower in the Dex group than the control group at T4, 8 h after the operation (T5), and 24 h after the operation (T6) (P <0.01). The Dex group required less time for mechanical ventilation than the control group (P = 0.003). The study suggests that 0.50 µg/kg Dex pretreatment could reduce propofol use and the duration of mechanical ventilation, and confer myocardial protection without increased adverse events during cardiac valve replacement.

Effect of methoxymine on prevention and treatment of myocardial injury and cardiac function in elderly patients with hypotension during intraspinal anesthesia.

We aimed to investigate the effects of methoxamine to prevent hypotension in the elderly with intraspinal anesthesia (IA) on myocardial injury and cardiac function. A retrospective study was conducted by enrolling sixty elderly patients who underwent femoral head replacement (FHR) under IA in our hospital from August 2019 to August 2020. The patients were divided into two groups according to the random number table method. In the control group (CG) (30 patients), 5 mg of ephedrine was administered sedately when patients developed hypotension (20% below basal blood pressure). In the research group (RG) (30 cases), 2 μg/(kg·h) of methoxamine hydrochloride was given as a constant-rate pump before anesthesia, and 1 mg of methoxamine hydrochloride was administered intraoperatively if hypotension occurred. The hemodynamic [systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR)], myocardial injury indexes [cardiac troponin I (cTnI), creatine kinase isoenzyme MB (CK-MB), fatty acid binding protein (FABP), plasma amino-terminal brain natriuretic peptide precursor (NT-proBNP)], cardiac function indexes [systemic vascular resistance (SVR), stroke volume (SV), net percentage ejection time (ET)] were observed before anesthesia (T1), at the end of surgery (T2), and 6 h after surgery (T3) in both groups. The Bruggemann Comfort Score (BCS) and Visual Analog Scale (VAS) scores at T3, 12 h postoperatively (T4) and 24 h postoperatively (T5) in both groups were observed, and the incidence of adverse reactions to intralesional anesthesia in both groups was counted. SBP, DBP and HR at T2 were lower than those at T1 in both groups, and SBP, DBP and HR at T3 were higher than those at T2, and SBP, DBP and HR at T2 and T3 in the RG were higher than those in the CG (p<0.05). In both groups, cTnⅠ, CK-MB and FABP were higher at T2 and T3 than at T1, higher at T3 than at T2, and NT-proBNP was higher at T2 than at T1 and T3, and lower in the RG than in the CG (p<0.05). In both groups, SVR and SV at time point T2 were lower than at time point T1 and ET was higher than at time point T1, SVR and SV at time point T3 were higher than at time point T2 and ET was lower than at time point T2, SVR and SV in the RG were higher than in the CG and ET was lower than in the CG (p<0.05). VAS scores were higher in both groups at T4 and T5 than at T3, and lower in the RG than in the CG (p<0.05). Methoxamine can effectively reduce the risk of hypotension in geriatric endotracheal anesthesia, which can reduce myocardial injury and stabilize cardiac function in patients.

Vascular endothelial growth factor-D plasma levels in fluid overload and cardiac function evaluation of elderly patients with cardiovascular disease.

This study aimed to investigate the clinical significance of vascular endothelial growth factor (VEGF) subtypes and growth differentiation factor-15 (GDF-15) plasma levels in evaluating the fluid overload and cardiac function of elderly patients with cardiovascular disease. The plasma levels of VEGF-C, VEGF-D, and GDF-15 were measured using ELISA. Their correlations with N-terminal pro B-type natriuretic peptide (NT-Pro BNP) and echocardiography data were analyzed. 1. Higher plasma levels of VEGF-D and GDF-15 were observed in elderly patients with cardiovascular disease and heart failure(P < .01). VEGF-D plasma levels were higher in patients with chronic heart failure than those with acute myocardial infarction (P < .01). VEGF-D plasma levels were positively correlated with amino-terminal pro-B type natriuretic peptide (NT-pro BNP) (P < .001). VEGF-D plasma levels were positively correlated with echocardiographic parameters, including left atrial diameter, left ventricular end-diastolic diameter and left ventricular ejection fraction, in patients with cardiovascular disease (P < .01). 2. VEGF-C plasma levels were higher in acute myocardial infarction group (P < .05). The plasma levels of VEGF-C were not correlated with either VEGF-D or NT-pro BNP plasma levels. VEGF-C plasma levels had no correlation with echocardiographic parameters. 3. GDF-15 plasma levels were positively correlated with sera biomarkers of cardiac injury (creatine kinase isoenzyme MB and cardiac troponin I). GDF-15 plasma levels were positively correlated with urinary biomarkers of tubular injury (N-acetyl-β-galactosidase and α1-microglobulin). Both GDF-15 and NT-pro BNP plasma levels were correlated with age, estimated glomerular filtration rate (eGFR), and nutritional biomarkers (albumin and hemoglobin plasma levels). VEGF-D plasma levels is a potential biomarker of fluid overload and cardiac function in elderly patients with cardiovascular disease. Age, nutrition, and kidney injury are factors influencing both GDF-15 and NT-pro BNP plasma levels in estimating cardiac function and fluid overload.